Temozolomide is active in childhood,progressive, unresectable,low-grade gliomas

PURPOSE: To assess the activity and tolerability of temozolomide in children with progressive low-grade gliomas (LGGs). PATIENTS AND METHODS: The authors reviewed the records of 13 children (6 months to 19 years old) with progressive LGGs and magnetic resonance imaging evidence of unresectable tumors who were treated with temozolomide at the authors' institution since 1999. RESULTS: Four patients received a 5-day regimen of temozolomide (150 mg/m2 per day) repeated every 28 days, and nine patients received a 42-day regimen (75 mg/m2 per day) repeated every 56 days. Three patients demonstrated partial responses to temozolomide, with a median time to maximal response of 5 months (range 4-12 months), and one had a minor response at 9 months. Four patients developed progression while on temozolomide, with a median time to progression of 7 months (range 1-12 months). Five patients had disease stabilization. Among the five patients with prior chemotherapy and/or radiation therapy, temozolomide was associated with disease stabilization in three and tumor response in one. In the three patients with neurofibromatosis type 1, two patients experienced tumor responses and one disease stabilization. Thrombocytopenia, nausea, emesis, and fatigue were the most common toxicities. Four patients discontinued therapy because of the side effects. CONCLUSIONS: Temozolomide is active in children with LGGs. It is effective in previously treated patients and in patients with neurofibromatosis type 1. The 42-day regimen appears less toxic than the 5-day regimen. Any impact on survival for these patients remains to be demonstrated.     

Chemotherapy for progressive low-grade gliomas in children older than ten years: the Dana-Farber experience

The purpose of this retrospective study was to examine the clinical and radiographic response rates to and toxicity of chemotherapy for low-grade gliomas in children older than 10 years of age. Between June 1999 and January 2001, seven consecutive children between the ages of 10 and 18 were treated with vincristine and carboplatin ± thioguanine, procarbazine, CCNU [lomustine], and vincristine (TPCV) for progressive low-grade gliomas. All 7 children completed a 10-week induction course of vincristine and carboplatin; 3 were switched to TPCV during the maintenance phase of therapy after developing an allergic reaction to carboplatin. Overall, 4 patients had a radiographic response to treatment with chemotherapy (3 partial responses and 1 minor response: objective response rate of 57%), and 2 more showed stable disease. One patient progressed while on treatment and 1 patient progressed off treatment, and after 31 months had elapsed. The resulting progression-free survival at the time of this report was 71%. The median duration of follow-up was 32 months (range 25-42 months). Hematologic toxicity was common, but did not result in cessation of therapy. No other significant treatment-related toxicities were observed. The results suggest that the clinical response/disease stabilization rate in children older than 10 years of age does not differ markedly from that observed in younger children. A prospective clinical trial of chemotherapy for progressive low-grade gliomas in children older than 10 years is therefore warranted.     

Chemotherapy: low-grade gliomas of the hypothalamus and thalamus

Chemotherapy is an increasing component of the management of diencephalic gliomas. It can result in tumor shrinkage and significant disease control in some patients. However, decisions concerning the institution of treatment should be based on the goals of treatment. Factors include: (1) age of the patient; (2) whether the child has neurofibromatosis type 1; (3) tumor size and location; (4) the potential sequelae of radiotherapy, and (5) the acute and long-term toxicity of the chemotherapeutic approach utilized. The erratic natural history of diencephalic tumors confounds evaluation of efficacy of the regimen chosen.     

A phase 2 feasibility study of sequential, dose intensive chemotherapy to treat progressive low-grade gliomas in children

BACKGROUND: Low-grade gliomas (LGGs) comprise nearly 35% of pediatric brain tumors and often occur in young children. Many cannot be resected and radiation therapy can be associated with excessive toxicity in children. Centrally located tumors in young children, and those that progress after radiation remain therapeutic challenges. This phase 2 feasibility trial investigated dose intense, sequential chemotherapy in children with LGG. PROCEDURE: Ten patients less than 21 years of age with progressive LGGs were enrolled. Courses 1 and 4 consisted of carboplatin and etoposide; courses 2 and 5 consisted of cyclophosphamide and vincristine; courses 3 and 6 consisted of lomustine, procarbazine, and vincristine. Dose adjustments were made to maximize dose intensity but minimize toxicity. RESULTS: Fifty-five of 60 planned chemotherapy courses were administered in 10 patients. One patient with stable disease after 3 courses had complete surgical resection. Two patients taking anticonvulsants experienced prolonged myelosuppression, necessitating removal from study after 5 chemotherapy courses. During 5 of 6 chemotherapy courses, more than 80% of the planned chemotherapy dose intensity was delivered. Two patients had complete responses, 2 patients had partial responses, 3 patients had minor responses, and 3 patients had disease stabilization. No children had life threatening infection or hemorrhage. No patient experienced progressive disease during therapy. CONCLUSIONS: Administration of sequential, dose intense chemotherapy was feasible and clinically tolerated. Concurrent anticonvulsant therapy limited dose intensity in 2 patients. Although efficacy appeared consistent with published larger series, small patient number in this study precludes definitive conclusions.     

Visual improvement despite radiologically stable disease after treatment with carboplatin in children with progressive low-grade optic/thalamic gliomas

BACKGROUND: The purpose of this study was to examine the clinical and radiologic response to carboplatin by children with progressive optic/thalamic gliomas. PATIENTS AND METHODS: Between July 1997 and July 1999, 12 consecutive children were treated with monthly carboplatin for progressive optic/thalamic gliomas. RESULTS: Five children have completed 12 cycles of carboplatin and five children are currently receiving treatment. Two children had progressive disease noted both clinically and radiologically. Nine children have stable radiologic disease and one child has had a partial radiologic response to chemotherapy. Eight children have had regular visual assessments. Four children (three with stable radiology and one with a partial radiologic response) have had improvement in their vision. Three children with radiologically stable disease have had no change in vision. One child has had deterioration in vision despite radiologically stable disease. CONCLUSIONS: The results suggest that the clinical response of optic/thalamic gliomas to carboplatin, as measured by visual acuity and visual fields, may be better than predicted by radiologic assessment. These data suggest that a prospective clinical study is warranted of the role of carboplatin in children with progressive optic/thalamic gliomas and visual impairment.     

Novalis radiosurgery of optic gliomas in children: preliminary report

AIM: To evaluate the effectiveness of Novalis radiosurgery (RS) in children with optic gliomas. METHODS: Four pediatric patients (1 male and 3 female) were treated for optic gliomas with Novalis RS in our institution between February 2002 and July 2002. Their mean age was 12 (range 5-16) years at presentation for Novalis RS. The mean target dose was 44 (range 41-45) Gy, with a mean fractionation dose of 1.58 (range 1.5-1.65) Gy. Follow-up included magnetic resonance imaging and ophthalmologic and endocrine examinations. RESULTS: The mean follow-up period was 54 (range 50-58) months. During the follow-up period, all patients were alive. Local control of the tumor was obtained in all patients. None of the patients showed clinically relevant morbidity, especially endocrine dysfunction. CONCLUSIONS: Novalis RS may be an excellent treatment method for optic gliomas in children. However, long-term follow-up is required for further evaluation of efficacy and potential side effects.     

Cyclophosphamide for the treatment of progressive low-grade astrocytoma: a Pediatric Oncology Group phase II Study.

PURPOSE: Results of a phase II trial of cyclophosphamide (CPM) for children with progressive low-grade astrocytoma are reported. PATIENTS AND METHODS: Fifteen patients with a median age of 39 months (range, 2 to 71) were included in this study. The tumors of 11 children were located in the optic pathway, hypothalamus, or thalamus. Four courses of intravenous CPM 1.2 g/m2 were administered every 3 weeks during the upfront window portion of this protocol. Subsequently, chemotherapy was to continue with CPM, vincristine, and carboplatin for 2 years. RESULTS: By study design, the first 14 patients were centrally reviewed after completion of the initial 4 CPM courses. Toxicity was primarily hematologic. One patients had a complete response, 8 had stable disease, and 5 had progressive disease (PD). The excessive number of children with PD prompted study closure. CONCLUSION: CPM as used in this protocol showed insufficient activity against astrocytoma to justify further patient accrual.     

Successful chemotherapy for congenital malignant gliomas: a report of two cases

We describe the cases of 2 patients with a congenital malignant glioma that responded to chemotherapy. In the first case, a 2-month-old boy had a conjugate deviation to the right side and nystagmus. A T(1)-weighted gadolinium-enhanced magnetic resonance image showed a large tumor in his right frontal lobe. The tumor was partially resected, and the histological diagnosis was malignant ganglioglioma. The child then underwent 6 cycles of chemotherapy (mainly carboplatin and etoposide), and the residual tumor shrank. The tumor was then partially resected during a second operation, after which the patient underwent 5 cycles of chemotherapy (a combination of carboplatin, etoposide, vincristine, ifosfamide, cisplatin and cyclophosphamide). The tumor has not recurred in more than 8.5 years. In the second case, a 2-month-old boy had bulging of the anterior fontanel. The T(1)-weighted gadolinium-enhanced magnetic resonance image showed a large suprasellar tumor. The tumor was partially resected, and the histological diagnosis was anaplastic astrocytoma. The patient underwent 8 cycles of chemotherapy (MCNU, carboplatin and etoposide) and the tumor has not recurred in more than 7.5 years. Our experience indicates that, if surgical removal and chemotherapy are done aggressively for malignant gliomas in neonates and infants, long-term survival is possible.     

Effect of psychosocial stimulation on mental development of severely malnourished children: an interim report

The effect of adding psychosocial stimulation to the treatment of severely malnourished children was studied. The study period covered children from the time they left the hospital to 24 months later. The children's developmental levels (DQs) were compared with those of two other groups who were in the hospital--an adequately nourished group with diseases other than malnutrition, and a severely malnourished group who received standard hospital care only. The children receiving intervention had structured play sessions in the hospital and were visited weekly for 2 years after returning home. During the visits paraprofessionals showed mothers how to continue structured play with their children. The malnourished children who did not receive intervention showed a marked deficit in developmental level compared with that of control children throughout the study. The control children showed a decline in developmental level with age, which is characteristic of disadvantaged children. The children receiving intervention showed marked improvements and by 24 months were ahead of the children who did not receive intervention in every subscale and were head of the adequately nourished children in two subscales. Both groups of malnourished children remained behind the control children in nutritional status and locomotor development.     

Tamoxifen and carboplatin for children with low-grade gliomas: a pilot study at St. Jude Children's Research Hospital

PURPOSE: The authors conducted a single-arm, prospective study using tamoxifen and carboplatin for the treatment of children with progressive or symptomatic low-grade gliomas. PATIENTS AND METHODS: Fourteen children with consecutively diagnosed cases of low-grade glioma were enrolled in this Study; all patients were younger than 14 years. One patient was excluded after induction chemotherapy because of the diagnosis of a nonmalignant condition. Patients were treated with daily tamoxifen (20 mg/m2 administered twice per day) in addition to targeted, monthly intravenous carboplatin at an area under the curve (AUC) exposure of 6.5 mg/mL x minute for 1 year or until they had clinical or radiologic evidence of disease progression. RESULTS: The median age at diagnosis was 5.3 years, the median age at initiation of chemotherapy was 8.3 years. Eight patients had tumors of the hypothalamus/optic pathway, two patients had thalamic tumors, and one patient each had tumors in the temporal lobe, tectum, and brain stem. Tumor histologic findings included fibrillary astrocytoma (n = 2), juvenile pilocytic astrocytoma (n = 6), and oligodendroglioma (n = 1). The best response to therapy was a partial response in two patients, stable disease in nine patients, and progressive disease in two patients. The overall survival at 3 years is 69%. The 3-year progression-free survival is 47%. Tamoxifen and carboplatin chemotherapy did not result in a significant number of objective responses in children with low-grade gliomas. The progression-free survival is similar to that of other published series. Nonmyelosuppressive agents such as tamoxifen deserve additional evaluation in the treatment of children with low-grade gliomas.     

进行性骨化性纤维发育不良一例

患儿女 ,13岁。因全身多部位反复出现条索状肿块 7年 ,弯腰、抬臂等活动受限 3个月 ,于 2 0 0 2年 6月就诊。患儿3岁时 ,右耳上方出现一蚕豆大小凸出物 ,质硬 ,无疼痛 ,2星期后自行消失。 6岁时 ,双侧膝关节内侧上下方皆出现条索状的肿块 ,15cm× 4cm大小 ,质硬 ,表面皮肤不红、不热 ,无疼痛感 ,无触痛 ,不影响关节活动。当地医院拟诊骨软骨瘤 ,7岁时行双腿骨软骨瘤切除术 ,术后病理切片示“良性骨软骨瘤”。术后 1年复发 ,双侧膝关节内侧又长出条块状肿物 ,体积较前次增大 ,伴疼痛 ,并出现右腿内翻、弯曲 ,活动受限(下蹲困难 ,呈半蹲状 )。…     

Trans-catheter closure of patent ductus arteriosus in childhood--an alternative to surgical ligature]

Transcatheter closure of a persistently patent ductus arteriosus (PDA) was successfully performed in four children using a Rashkind double disk umbrella device. Mean age was 5.1 +/- 1.5 (2.8 to 6.3 years) and weight 18.8 +/- 3.8 kg (14.1 to 22.3 kg). In all children the PDA was the only cardiac lesion and was diagnosed clinically and by means of continuous wave and color-coded doppler echocardiography. After angiographic measurement of PDA size the correlating device was implanted. The ductus was closed immediately in two children, whereas there was a residual angiographic shunt in the others. Echocardiography performed within 24 hours showed a minimal shunt only in one of these cases. The shunt had disappeared at the one month follow up study. We experienced none of the reported possible complications. Transcatheter closure of the PDA after the neonatal period seems to be a safe and effective alternative to surgical ligation as our early experience shows, and should become the procedure of first choice in these patients.     

Changes in body composition and bone density after discontinuation of growth hormone therapy in adolescence: an interim report

Growth hormone deficiency (GHD) in adults and children is associated with decreased lean tissue mass (LTM), increased fat mass and reduced bone mineral density (BMD). The changes in BMD and body composition, 6 and 12 months after ceasing GH treatment, were assessed using dual-energy X-ray absorptiometry in eight patients with GHD (age range, 13.8–17.5 years). Seven age-matched normal subjects who had completed growth were assessed at 0 and 12 months. Total body BMD was low at baseline ( p < 0.05) in patients with GHD compared with the predicted values based on sex-specific regression equations, with height, weight and age taken into account. Total body, lumbar spine and femoral neck BMD increased in the patients and controls at 12 months. LTM decreased significantly by a mean of 1.37 kg in the patients with GHD at 12 months whereas there was a non-significant increase in LTM in the control group. The percentage of body fat increased in all patients with GHD at 6 and 12 months, from 27.2 ± 11% (mean ± SD) at baseline to 32 ± 9.9% at 12 months ( p = 0.009). There was no significant increase in mean percentage body fat in the control group. The ratio of android (trunk):gynoid (legs) fat was calculated using default settings of dual-energy X-ray absorptiometry. The mean android:gynoid fat ratio increased, though non-significantly, in patients with GHD at 12 months, with 6 of 7 showing an increase; no change was observed in the control group. These results indicate that BMD continues to increase 12 months after ceasing GH therapy in adolescents with GHD, but that unfavourable alterations in body composition occur.     

Variability in the Proteus syndrome: report of an affected child with progressive lipomatosis

In 1983 the Proteus syndrome was delineated by Wiedemann et al. [12]. We report a 10-month-old girl, a further child affected by the new syndrome. The typical signs are macrodactyly, hemihypertrophy, pigmented nevi, hyperkeratosis, and subcutaneous hamartomatous tumours. Our patient shows an aggressive lipomatosis on the trunk and local relapses after surgical interventions in the regions involved. Histology of the adipose tissue showed considerable anisocytosis and increased cell volume.     

症状前期进行性肌营养不良患儿24例病例系列报告

背景：进行性肌营养不良（PMD）中Duchenne型肌营养不良(DMD)和Becker型肌营养不良(BMD)的临床表现、治疗和预后差异明显,目前国内外对症状前期PMD患儿的诊断尚无共识。 目的：探讨婴幼儿时期症状前期PMD患儿的临床特征和实验室检查特点,并探讨血清肌酶水平在DMD和BMD分型诊断中的价值。 设计：病例系列报告。 方法：收集2016年1月至2020年7月江西省儿童医院确诊的症状前期PMD患儿,分析临床特征和实验室检查特点,并以基因检测结果为诊断标准分为DMD组和BMD组,血清肌酶通过ROC曲线分析以约登指数最大值时的取值作为诊断界值,比较不同肌酶的诊断准确性。 主要结局指标：PMD患儿的临床表现、基因结果、血清酶水平（AST、ALT、LTH、CK、CK-MB）。 结果：24例PMD患儿纳入分析,其中DMD组18例,BMD组6例。22例（91.7%）因发现转氨酶升高就诊,2例（8.3%）因亲戚确诊前来就医。PMD患儿CK-MB、CK、LDH、AST和ALT水平均明显升高,DMD组均高于BMD组（除AST外,P均<0.05）。当ALT>224.5 U·L-1、CK>11 069 IU·L-1、CK-Mb>204 IU·L-1、LDH>1 349.5 IU·L-1时为DMD的可能性更高,尤其是LDH>1 349.5 IU·L-1具有高度特异性。 结论：血清肌酶水平增高为 PMD 患儿症状前期的主要表现。LDH＞1 349.5 IU·L-1对诊断DMD具有高度特异性。